7B3E

Crystal structure of myricetin covalently bound to the main protease (3CLpro/Mpro) of SARS-CoV-2

7B3E の概要

• エントリーDOI: 10.2210/pdb7b3e/pdb
• 分子名称: Main Protease, 1,2-ETHANEDIOL, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: sars-cov-2, mpro, 3clpro, exscalate4cov, drug discovery, elettra, viral protein, myricetin
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68966.69

構造登録者

Costanzi, E.,Demitri, N.,Giabbai, B.,Storici, P. (登録日: 2020-11-30, 公開日: 2021-01-13, 最終更新日: 2025-10-01)

主引用文献

Kuzikov, M.,Costanzi, E.,Reinshagen, J.,Esposito, F.,Vangeel, L.,Wolf, M.,Ellinger, B.,Claussen, C.,Geisslinger, G.,Corona, A.,Iaconis, D.,Talarico, C.,Manelfi, C.,Cannalire, R.,Rossetti, G.,Gossen, J.,Albani, S.,Musiani, F.,Herzog, K.,Ye, Y.,Giabbai, B.,Demitri, N.,Jochmans, D.,Jonghe, S.,Rymenants, J.,Summa, V.,Tramontano, E.,Beccari, A.R.,Leyssen, P.,Storici, P.,Neyts, J.,Gribbon, P.,Zaliani, A.
Identification of Inhibitors of SARS-CoV-2 3CL-Pro Enzymatic Activity Using a Small Molecule in Vitro Repurposing Screen.
Acs Pharmacol Transl Sci, 4:1096-1110, 2021

PubMed Abstract: Compound repurposing is an important strategy for the identification of effective treatment options against SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (3CL-Pro), also termed M-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyproteins pp1a and pp1ab at multiple distinct cleavage sites. We here report the results of a repurposing program involving 8.7 K compounds containing marketed drugs, clinical and preclinical candidates, and small molecules regarded as safe in humans. We confirmed previously reported inhibitors of 3CL-Pro and have identified 62 additional compounds with IC values below 1 μM and profiled their selectivity toward chymotrypsin and 3CL-Pro from the Middle East respiratory syndrome virus. A subset of eight inhibitors showed anticytopathic effect in a Vero-E6 cell line, and the compounds thioguanosine and MG-132 were analyzed for their predicted binding characteristics to SARS-CoV-2 3CL-Pro. The X-ray crystal structure of the complex of myricetin and SARS-Cov-2 3CL-Pro was solved at a resolution of 1.77 Å, showing that myricetin is covalently bound to the catalytic Cys145 and therefore inhibiting its enzymatic activity.

PubMed: 35287429
DOI: 10.1021/acsptsci.0c00216

実験手法

X-RAY DIFFRACTION (1.77 Å)